The goal of the Program in Structural and Chemical Biology Is to provide a molecular description and interpretation of biological processes associated with oncogenesis and tumor progression. Together, the tools of structural and chemical biology permit investigation of fundamental aspects of cancer biology, the design of small molecule probes for biological discovery, the design and synthesis of small molecule therapeutics, and development of novel molecular and cellular technologies. Program members include those with expertise in organic synthesis, chemical biology. X-ray crystallography and NMR analyses, enzymology, and modeling at the molecular level. Program members provide valuable consultation and technology to other Cancer Institute investigators who have identified molecules involved in cellular transformation, and this serves to stimulate the exchange of technology and expertise between members of the Program as well as with other members of the Cancer Institute. Program members have provided the leadership for a number of Initiatives that have markedly enhanced the technological capabilities available to the cancer community at Duke, Including the upgrade and expansion of our X-ray crystallography and NMR facility, establishment of a state-of-the-art proteomics facility, and the establishment of core facilities that provide small molecule synthetic capabilities and enable high-throughput screening of small molecule libraries. The Program includes 21 members from 6 basic and clinical departments within Duke University. Total funding for program members is $10,652,507, of which $8,709,205 is from peer- reviewed sources. A cancer focus is illustrated by $1,322,160 or 15.2% of funding from the NCI, the American Cancer Society or the Department of Defense. From 2004-2008, program members published 432 papers in peer-reviewed journals cited in PubMed. Of these publications, 8% are the result of intra-programmatic collaborations and 8% due to Inter-programmatic collaborations.